Study of the BTK (Bruton\'s Tyrosine Kinase) in patients with congenital agammaglobulinemia.

Author(s)

Rosana Rezende de Oliveira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2008-10-01

Examining board members

Magda Maria Sales Carneiro Sampaio; Jose Alexandre Marzagao Barbuto; Carlos Alberto Moreira Filho; Maria Notomi Sato; Dirceu Solé

• Advisor: Magda Maria Sales Carneiro Sampaio
• Field of knowledge: Health Sciences - Medicine
• Indexed in: Banco de Dados Bibliográficos da USP-DEDALUS; Biblioteca Digital de Teses e Dissertações - USP
• Location: Universidade de São Paulo. Biblioteca do Instituto de Ciências Biomédicas; T-ICB BIOT QH323.6; O48eg

Abstract

X-linked Agammaglobulinemia (XLA) is a primary immunodeficiency characterized by the absence or decreased numbers of mature B cells in peripheral blood, and by a lack of all immunoglobulin isotypes, leading to an increased susceptibility to severe bacterial and enteroviral infections. XLA is caused by mutations in the gene encoding for Bruton\'s tyrosine kinase (BTK), a protein member of the Tec family of cytoplasmic tyrosine kinases and plays a vital modulation role in many cellular processes. In this study thirty-three patients were analyzed for the presence of BTK mutations by SSCP/HA and sequencing. The expression analysis was carried out by the technique of Real-Time PCR. It was found mutations of the stop codons type, amino acid substitutions, splice defects, small deletions/insertions and frameshift in these patients affecting the PH, SH3, SH2 and tyrosine kinase domains of protein. The expression levels were very low in the patients with stop codon mutations, and in the other mutations, the expression levels were about 15% and were correlated with the mutation types. (AU)